Stenbit A E, Tsao T S, Li J, Burcelin R, Geenen D L, Factor S M, Houseknecht K, Katz E B, Charron M J
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Nat Med. 1997 Oct;3(10):1096-101. doi: 10.1038/nm1097-1096.
GLUT4, the insulin-responsive glucose transporter, plays an important role in postprandial glucose disposal. Altered GLUT4 activity is suggested to be one of the factors responsible for decreased glucose uptake in muscle and adipose tissue in obesity and diabetes. To assess the effect of GLUT4 expression on whole-body glucose homeostasis, we disrupted the murine GLUT4 gene by homologous recombination. Male mice heterozygous for the mutation (GLUT4 +/-) exhibited a decrease in GLUT4 expression in adipose tissue and skeletal muscle. This decrease in GLUT4 expression did not result in obesity but led to increased serum glucose and insulin, reduced muscle glucose uptake, hypertension, and diabetic histopathologies in the heart and liver similar to those of humans with non-insulin-dependent diabetes mellitus (NIDDM). The male GLUT4 +/- mice represent a good model for studying the development of NIDDM without the complications associated with obesity.
GLUT4，即胰岛素反应性葡萄糖转运蛋白，在餐后葡萄糖代谢中起重要作用。GLUT4活性改变被认为是肥胖和糖尿病患者肌肉及脂肪组织中葡萄糖摄取减少的原因之一。为评估GLUT4表达对全身葡萄糖稳态的影响，我们通过同源重组破坏了小鼠GLUT4基因。突变杂合子（GLUT4+/-）雄性小鼠脂肪组织和骨骼肌中的GLUT4表达降低。GLUT4表达的这种降低并未导致肥胖，但导致血清葡萄糖和胰岛素水平升高、肌肉葡萄糖摄取减少、高血压以及心脏和肝脏出现与非胰岛素依赖型糖尿病（NIDDM）患者相似的糖尿病组织病理学变化。雄性GLUT4+/-小鼠是研究无肥胖相关并发症的NIDDM发病机制的良好模型。
